Medical Expulsive Therapy is Underused for the Management of Renal Colic in the Emergency Setting - Beyond the Abstract

MEDICAL expulsive therapy is a noninvasive method used to manage ureteral stones. Several types of MET are available in the ED setting, of which the a-adrenoreceptor antago- nist (a-blocker) tamsulosin has been the most studied. The principal mechanism of action of a-blockers includes relaxing the smooth muscle of the ureter, allowing for passage of the stone. Several trials have demonstrated the efficacy of MET in the facilitation of spontaneous passage of stones in the ureter. These studies have shown that MET is associated with a higher passage rate, quicker time to passage and lower requirement of analgesics. Other benefits of MET include the fact that it is a low cost option compared to invasive procedures. Direct comparison of tamsulosin with calcium channel blockers such as nifedipine have been mixed with several studies showing similar efficacy in expulsion rates and others demonstrating better outcomes for a-blockers. There is also evidence that a-blockers are associated with a lower inci- dence of complications than calcium channel blockers. However, recently a large randomized, controlled trial revealed that MET provided no outcome benefit when comparing groups treated with tamsulosin, nifedipine or placebo by the requirement for additional intervention.  The benefits of MET seem unclear with such conflict- ing data.
Although advantages of MET have been demon- strated, its use in the ED setting has been low. In a survey of ED physicians in 2008 only 63% had used MET in practice.  Furthermore, while the 2007 AUA guidelines established MET with a-blockers as first line medical therapy for ureteral stones less than 10 mm, in practice only 22% of patients with ureteral stones may receive the medication.  The primary objective of this study was to determine adherence to the AUA guidelines of sug- gested management of ureteral calculi with MET. The secondary objective was to determine outcomes in patients treated with MET.

With institutional review board approval we retrospec- tively analyzed the records of ED visits at hospitals in our health system between December 2010 and May 2013. We included a total of 2,105 patients with suspected urolithi- asis identified by an ICD-9 code for urolithiasis (592, 592.0 and 592.1) who also underwent unenhanced CT during the ED visit.
Data on patient demographics, ED course including a 10-point VAS for pain and hospital discharge pre- scriptions were collected. Patient charts were analyzed for outcomes within 12 weeks of the initial ED visit. After discharge from the ED if telephone or visit records indi- cated the exact date of passage, time to expulsion was calculated. If no exact date was available but the patient was specifically noted to have passed the stone sponta- neously or passage was confirmed by imaging, this was categorized as spontaneous passage. Patients with a stone initially diagnosed on CT who subsequently had evidence of passage in note or on imaging, or who underwent a procedures included cystoscopy with stent placement, extracorporeal shock wave lithotripsy, ureteroscopy or percutaneous nephrolithotomy. When detailed informa- tion on the definitive outcome was not available for a patient, the patient was considered LTF. Patients were excluded from study if they had undergone a urological procedure within 30 days of the ED visit.
At the time of the ED visit CT scans were initially read by a radiologist. For study purposes CT scans were independently confirmed by a blinded urologist who characterized the size and location of each stone. Under high magnification stone size was determined by measuring the stone in its largest diameter in the axial plane. Ureteral stone location was defined as the prox- imal ureter if it was proximal to the sacroiliac joints, the middle ureter if it was located over the sacroiliac joints and the distal ureter if it was distal to the sacroiliac joints.
Continuous means were evaluated by the 2-tailed independent t-test while the chi-square test was used to evaluate categorical data. VAS pain scores were evaluated with the 2-tailed Mann-Whitney test. Numerical variables are expressed as the mean ± SD. Significance was considered at p <0.05.

The records of 2,105 patients were analyzed. Ure- teral stones were found in 1,028 patients (48.8%). MET was prescribed for 50.0% of patients with ureteral stones. Patients prescribed a MET regimen were given 0.4 mg tamsulosin daily except 2 who received doxazosin 1 mg daily. Additionally 7.2% of the 1,077 patients with no evidence of ureteral stones were prescribed an a-blocker. Patients with ureteral stones were older, more likely to be male and had higher initial VAS pain scores (table 1). Patients with no evidence of ureteral stones were equally as likely to have renal stones.
In patients with ureteral stones identified on unenhanced CT there were no significant differ- ences in age, gender, serum creatinine or initial pain score between those who did vs did not receive MET (table 2). Stone location and size were similar in the 2 groups. Furthermore, time spent in the ED, pain scores at discharge home and the presence of concurrent renal stones were also similar.

Definitive followup was available in 488 patients (47.5%) with ureteral stones (see figure). The rate of LTF was similar in the MET and no MET groups (54.9% and 51.0%, respectively). There was no sta- tistically significant difference in the rate of requirement for surgical intervention between groups (table 2). The definitive date of stone passage was available for 44 patients with ureteral stones who did not receive MET and 53 who received MET. Patients treated with MET who had a documented date of stone passage achieved a shorter time to spontaneous passage (7.1 vs 12.8 days, p ¼ 0.0477). Of patients who required procedures 83.9% who received MET required ureteroscopy compared to 79.8% who did not receive MET (p ¼ 0.19). Of pa- tients who required a procedure 14.6% of the MET group underwent extracorporeal shock wave litho- tripsy and 1.5% underwent cystoscopy with stent placement compared to 14.3% and 5.9%, respec- tively, who did not receive MET and required a procedure. There was no difference in the rate of return to the ED for flank pain after the initial visit. Overall distal stones had a higher rate of spon- taneous passage than middle and proximal stones (57.8% vs 28.3% and 36.8, respectively, p ¼ 0.009). Small stone size (5 mm or less) was also associated with spontaneous passage (p <0.0001). On subset analysis MET was not associated with a higher rate of spontaneous passage according to ureteral location (distal, middle and proximal) or stone size 5 to 10 mm. On multiple logistic regression with a composite end point of a return ED visit or a urological procedure vs spontaneous passage statistically significant variables associated with spontaneous passage included stone size, distal stone location and younger age (p <0.0001, 0.0043 and 0.0119, respectively). MET prescription was not statistically significant in this analysis (p ¼ 0.27).

The total costs of treating urolithiasis in America annually exceeds $2 billion.15 Any strategy aimed at decreasing the need for interventions for urinary stones could greatly decrease health care costs. MET, which has been proposed as 1 such strategy, has been purported to reduce health care costs by aiding in the spontaneous passage of ureteral stones.
The primary objective of this study was to determine our institutional compliance with the 2007 AUA guidelines for managing ureteral stones in the ED. Surprisingly only half of patients with image proven ureteral stones had undergone MET by the time of discharge home. Another 7% of pa- tients received MET when they had no evidence of ureteral stones. These numbers suggest that implementation of the AUA guidelines has not been robust. There appears to be a gap between urologi- cal dogma and practical application by emergency medicine teams. At our institution we are looking into methods to better standardize care for patients seeking emergency care for ureteral colic through the collaborative development of care pathways.
However, the benefits of MET have been debated. In a recent study Pickard et al randomized 1,167 patients to placebo, tamsulosin or nifedipine.11 The investigators found no advantage that MET decreased the requirement for urological interven- tions in treatment groups compared to placebo at 4 and 12 weeks, and they found similar rates of spontaneous passage in the groups. Furthermore, they identified no difference in time to stone pas- sage or in pain. While the study may be critiqued for using a survey design rather than imaging modal- ities to document outcomes, it is the largest pro- spective trial testing the benefits of MET. These results are not unique as another recent prospective trial showed no overall benefit for MET after analyzing followup CT scans.16 Our results support the findings of these studies and demonstrate no advantage for MET in decreasing the rate of uro- logical procedures in patients with ureteral stones.

However, our results revealed an important outcome for MET in that it was associated with a shorter time to spontaneous stone passage. The primary objective of this series was to eval- uate adherence to guidelines in clinical practice and not the outcomes of medical expulsive therapy. Ours was a retrospective study in which we searched electronic medical records for evidence of sponta- neous stone passage and the requirement for uro- logical procedures. Not all patients had such information available and this is indeed a source of bias. It is likely that many patients who passed stones spontaneously and needed no procedure did not schedule followup visits or notify health care providers of such outcomes. If so, the true rate of spontaneous passage was likely higher in this population.
Although many patients were LTF by our strict criteria, requirement for a urological procedure was similar between the groups even when patients LTF were included in analysis, that is MET vs no MET 52.0% vs 52.2% in those with definitive followup and 25.5% vs 23.5% (p ¼ 0.46) in all patients with ureteral stones.
While evidence for the benefits of MET has been conflicting, many cited series have shown advan- tages such as shorter time to expulsion, and decreased pain and cost.5,7,9 Recently 2 publications suggested that MET may have limited value or may have specific roles only for stones larger than 5 mm.11,16 These studies have flaws but they have stimulated a reevaluation of our practices. Indeed our findings regarding MET outcomes may parallel some of the conclusions reached in these recent studies.
However, time to stone passage is a critical end point. As such many urologists would argue for the use of a-blockers in eligible patients with ureteral stones regardless of whether they reduce the requirement for invasive procedures. At our insti- tution a joint task force of ED and urology physi- cians has recently completed a care pathway that will be implemented. We plan to analyze the impact of its implementation.

MET with a-blockers may not alter the subsequent need for urological procedures in patients with ureteral stones. However, there is evidence that MET may hasten spontaneous passage of stones. Given this benefit, MET remains highly underused in the emergency setting in patients in whom im- aging demonstrates ureteral stones. Care should be taken to confirm that patients with ureteral calculi are provided with the optimal conditions for spon- taneous passage.

Written By: Christopher Loftus,* Yaw Nyame, Bryan Hinck, Daniel Greene, Hemant Chaparala, Kareem Alazem and Manoj Monga
From the Lerner College of Medicine (CL) and Glickman Urological and Kidney Institute (YN, BH, DG, MM), Cleveland Clinic and Case Western Reserve University School of Medicine (HC, KA), Cleveland, Ohio

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